Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical s...Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical symptoms closely resemble those of gastric adenocarcinoma.Because of its rarity,misdiagnosis and missed diagnoses are prevalent.Compared with gastric adenocarcinoma,HAS typically exhibits higher invasiveness and amore unfavorable prognosis.This review aimed to elaborate on the pathological features,potential mechanisms,clinical characteristics,diagnosis,and prognosis of HAS.The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.展开更多
Hepatoid adenocarcinoma of the stomach (HAS)is an extremely rare and unique gastric malignancy.The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis....Hepatoid adenocarcinoma of the stomach (HAS)is an extremely rare and unique gastric malignancy.The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis.We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016,as well as 294 cases reported prior to 2017 in research databases.Among these patients,45.6%(115/252)had lesions in the gastric antrum and 77.0%(235/305)were male.Elevated levels of serum alpha-fetoprotein (AFP)were detected in most patients(75/93,80.6%).Vascular invasion(199/286,69.6%),lymph node metastasis (222/283,78.4%),and preoperative distant metastasis (121/328,36.9%)were commonly observed.The 5-year disease-free survival (DFS)and disease-specific survival (DSS) were 20.7%and 29.2%,respectively.DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS:P<0.001, hazard ratio (HR)=-1.831,95%confidence interval (CI):0.060-0.429;DSS:P<0.001,HR=-2.185, 95%CI:0.032-0.401].In conclusion,HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer.Complete surgery,early pTNM stage,and adjuvant therapy may predict a more favorable prognosis.Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.展开更多
Hepatoid adenocarcinoma of the stomach (HAS) is a rare form of gastric cancer that has unique clinicopathological features and an extremely poor prognosis. Here, we report on three patients with suspected gastric canc...Hepatoid adenocarcinoma of the stomach (HAS) is a rare form of gastric cancer that has unique clinicopathological features and an extremely poor prognosis. Here, we report on three patients with suspected gastric cancer who were referred to our hospital. Gastrointestinal fiberscopy on the three patients revealed two lesions in the antrum and a third lesion in the gastroesophageal junction. The alpha fetoprotein (AFP) serum levels were markedly elevated in all cases. At the time of diagnosis, two cases were advanced stages with lymph nodes and/or liver metastases. Two patients underwent exploratory laparotomy. A total gastrectomy was performed on the operable lesion, and an expanded gastrectomy was completed in the case with hepatic metastases. Histopathological analysis revealed that the tumors displayed two pathological changes:hepatoid-like foci and adenocarcinomatous. Furthermore, the tumor cells were immunohistochemically positive for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. All three patients received chemotherapy. The follow-up duration ranged from 8-36 mo. Our experience and previous published studies have suggested that HAS is an aggressive type of adenocarcinoma. However, radical surgery and chemotherapy may positively impact clinical outcomes.展开更多
BACKGROUND The aim of the present study was to examine the clinical characteristics of hepatoid adenocarcinoma of the stomach (HAS) and its diagnosis,treatment,and prognosis.CASE SUMMARY A retrospective analysis of 13...BACKGROUND The aim of the present study was to examine the clinical characteristics of hepatoid adenocarcinoma of the stomach (HAS) and its diagnosis,treatment,and prognosis.CASE SUMMARY A retrospective analysis of 13 HAS cases was performed.The mean age of the 13patients was 66.08 years,and 10 of the 13 patients were male.Prior to treatment,the alpha-fetoprotein levels in the serum were elevated in 7 patients,the tumour was located in the distal or gastric body in 11 patients,and the gastroscopy pathological results showed that 3 patients had poorly differentiated tumours and that 8 patients had moderately/poorly differentiated tumours.Abdominal CT scans showed local stomach wall thickening,and enlarged lymph nodes were visible around the stomach in 8 patients.Of the 13 patients,11 underwent radical surgery.The clinical pathological staging was as follows:Stage Ⅱ in 2 cases;stage Ⅲ in 8 cases;and stage Ⅳ in 1 case.A total of 3 patients were lost to follow-up.Otherwise,as of the last follow-up,3 patients had survived for 56 mo,and the other 7 patients failed to achieve long-term survival (survival period of 1-56 mo).CONCLUSION HAS is a special type of gastric cancer,and the prognosis of HAS has improved compared with past prognoses.Measurement of alpha-fetoprotein,early diagnosis,active surgical treatment,and application of new diagnostic and treatment techniques are conducive to improving the prognosis of HAS.展开更多
AIM: To evaluate the dynamic computed tomography(CT) findings of liver metastasis from hepatoid adenocarcinoma of the stomach(HAS) and compared them with hepatocellular carcinoma(HCC).METHODS: Between January 2000 and...AIM: To evaluate the dynamic computed tomography(CT) findings of liver metastasis from hepatoid adenocarcinoma of the stomach(HAS) and compared them with hepatocellular carcinoma(HCC).METHODS: Between January 2000 and January 2015, 8 patients with pathologically proven HAS and liver metastases were enrolled. Basic tumor status was evaluated for the primary tumor location and metastatic sites. The CT findings of the liver metastases were analyzed for tumor number and size, presence of tumor necrosis, hemorrhage, venous tumor thrombosis, and dynamic enhancing pattern.RESULTS: The body and antrum were the most common site for primary HAS(n = 7), and observed metastatic sites included the liver(n = 8), lymph nodes(n = 7), peritoneum(n = 4), and lung(n = 2). Most of the liver metastases exhibited tumor necrosis regardless of tumor size. By contrast, tumor hemorrhage was observed only in liver lesions larger than 5 cm(n = 4). Three patterns of venous tumor thrombosis were identified: direct venous invasion by the primary HAS(n = 1), direct venous invasion by the liver metastases(n = 7), and isolated portal vein tumor thrombosis(n = 2). Dynamic CT revealed arterial hyperattenuation and late phase washout in all the liver metastases.CONCLUSION: On dynamic CT, liver metastasis from HAS shared many imaging similarities with HCC. For liver nodules, the presence of isolated portal vein tumor thrombosis and a tendency for tumor necrosis are imaging clues that suggest the diagnosis of HAS.展开更多
BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatme...BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatment plan needs further study.CASE SUMMARY In order to deeply understand the occurrence and development of HAL,here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation.The patient refused chemotherapy and received one course of treatment(immune checkpoint inhibitors),and died three months later due to progressive disease.CONCLUSION HAL is a special type of NSCLC.The surgical treatment of HAL in the limited stage can achieve long-term survival,but most of them were in the advanced stage when they were found,and the prognosis was poor,which requires multidisciplinary comprehensive treatment.展开更多
BACKGROUND Stomach adenocarcinoma(STAD)is one of the main reasons for cancer-related deaths worldwide.This investigation aimed to define the connection between STAD and Cuproptosis-related genes(CRGs).Cuproptosis is a...BACKGROUND Stomach adenocarcinoma(STAD)is one of the main reasons for cancer-related deaths worldwide.This investigation aimed to define the connection between STAD and Cuproptosis-related genes(CRGs).Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper.AIM To explore the identification of potential biomarkers for STAD disease based on cuproptosis.METHODS A predictive model using Gene Ontology(GO),Least Absolute Shrinkage and Selection Operator(LASSO),Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis analyzed gene interconnections,focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD.Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed.The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic,Kaplan-Meier curves,and COX regression analysis.Validation was conducted with datasets GSE26942,GSE54129,and GSE66229.Expression of copper-related differ-entially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas.RESULTS Three significant genes(FDX1,LIAS,MTF1)were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups.These genes were down-regulated in both risk categories.GO and KEGG analyses highlighted their involvement mainly in the electron transport chain.After validating their differential expression,FDX1 emerged as the most accurate diagnostic marker for gastric cancer.Additionally,the RCircos package localized FDX1 on chromosome 11.CONCLUSION Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy,providing new ideas for further scientific research.展开更多
Objective:We reported a case with AFP produced gastric hepatoid adenocarcinoma.Methods:A male patient,77 year-old,was admitted to our hospital due to an unreasonable elevation of serum AFP.The tumors were revealed by ...Objective:We reported a case with AFP produced gastric hepatoid adenocarcinoma.Methods:A male patient,77 year-old,was admitted to our hospital due to an unreasonable elevation of serum AFP.The tumors were revealed by PET-CT,but until the tumors were removed during the surgery,we did not recognize the primary lesion was the gastric cancer.Results:Radical distal gastrectomy was performed.The gastric lesion was confirmed by histology as a hepatic adenocarcinoma in its early stage.Conclusion:The rare etiology of the AFP elevation should be kept in mind in clinic,extrahepatic lesions should be excluded.展开更多
BACKGROUND Both hepatoid adenocarcinoma of the stomach(HAS)and neuroendocrine differentiation(NED)are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes.HAS ...BACKGROUND Both hepatoid adenocarcinoma of the stomach(HAS)and neuroendocrine differentiation(NED)are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes.HAS with NED is even rarer.CASE SUMMARY Here,we report a 61-year-old man with HAS with NED,as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule.Distal gastrectomy was performed,and pathological examination led to the diagnosis of HAS with NED.However,liver metastases occurred 6 mo later despite adjuvant chemotherapy,and the patient died 27 mo postoperatively.CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases.We first report the detailed processes of the treatment and development of HAS with NED,providing an important reference for the clinical diagnosis and treatment of this condition.展开更多
We describe the computed tomography(CT)imaging findings in six cases(five males and one female;age range 61-78 years;mean age 67.3 years)with histologically proven hepatoid adenocarcinoma of the stomach(HAS).Five of t...We describe the computed tomography(CT)imaging findings in six cases(five males and one female;age range 61-78 years;mean age 67.3 years)with histologically proven hepatoid adenocarcinoma of the stomach(HAS).Five of the six patients had elevated serum alpha-fetoprotein levels.The most common type of gross appearance HAS on CT is a polypoid mass(83%,5/6).The most common contrast enhancement pattern was heterogeneous.All six patients had a regional lymphadenopathy larger than 6 mm in its short axis.Liver metastases(n=3)were noted.Venous tumor thrombosis was identified in the portal vein(n=2)of the regions near primary gastric tumors or metastatic masses.Our findings suggest in an elderly,male patients with a large heterogeneous enhancement tumor,the presence of distant metastases,regional lymphadenopathy and characteristically increased serum alphafetoprotein levels indicates a high likelihood of HAS.展开更多
A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease(PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon,who was initially treated with a s...A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease(PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon,who was initially treated with a subtotal colectomy with ileostomy.One year later,the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis,as well as a markedly elevated serum level of alpha-fetoprotein(AFP).Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid adenocarcinoma.Subsequent review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic adenocarcinoma.The patient was subsequently treated with a cytotoxic regimen of FOLFOX(oxaliplatin,leucovorin,5-fluorouracil) and bevacizumab,with stable results being achieved after six months.This case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.展开更多
AIM: Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive be...AIM: Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS: Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT: Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions (mean follow-up period, 56 too). All 9 cases of EWDA could be classified into gastric phenotype (5 lesions) and intestinal phenotype (4 lesions). The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cellsand their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION: Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.展开更多
AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship ...AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.展开更多
BACKGROUND Hepatoid adenocarcinoma of the lung(HAL) is an extremely rare malignant tumor,and many patients with HAL exhibit high levels of alpha-fetoprotein(AFP) expression.Currently,there is no standardized treatment...BACKGROUND Hepatoid adenocarcinoma of the lung(HAL) is an extremely rare malignant tumor,and many patients with HAL exhibit high levels of alpha-fetoprotein(AFP) expression.Currently,there is no standardized treatment strategy for advanced HAL and its prognosis is poor.CASE SUMMARY We report a 55-year-old man with unresectable AFP-related HAL.The largest cross-sectional area of the mass in the upper lobe of the left lung at the beginning of treatment was 8.46 cm × 6.53 cm.The patient’s serum AFP level was 9283 ng/m L.The mass increased in size to 8.86 cm × 8.21 cm after two courses of platinum-based combination chemotherapy and immunotherapy,and serum AFP reached its highest level(71232.2 ng/m L).The patient was treated with sorafenib(400 mg twice daily,per os).Forty days later,the mass was reduced to 5.63 cm × 5.29 cm and serum AFP level dropped to 786.8 ng/m L.The patient achieved partial remission for > 9 mo with sorafenib and an excellent biomarker response,as well as survival > 13 mo,which is among the longest reported for unresectable stage IV HAL.CONCLUSION This is the first report to document successful treatment of unresectable AFPrelated HAL with single-agent sorafenib after multiline therapy.展开更多
BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is curren...BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is currently no standard treatment for this disease,which has a poor prognosis.CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis.He underwent first-line chemotherapy but that failed.Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment.The progression-free survival and overall survival were 14 mo and 16 mo,respectively,after treatment.In addition,the main adverse reaction was tolerable.The patient did not die of tumor progression.CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment.Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.展开更多
BACKGROUND Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease.Reports of malignant change of heterotopic pancreas are scarce.CASE SUMMARY A 44-year-o...BACKGROUND Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease.Reports of malignant change of heterotopic pancreas are scarce.CASE SUMMARY A 44-year-old Chinese female underwent a gastroscopy to assess abdominal distension that had persisted for 2 months.A protruding lesion in the gastric antrum was revealed but no malignant tissue was found in the biopsy specimen.The patient's symptom persisted and progressed to repeated vomiting.Endoscopy after 4 months revealed obstruction of the gastric outlet caused by the protruding lesion.A distal gastrectomy was performed.Histopathological examination of the surgical specimen showed the malignant transformation of aberrant pancreas in the stomach.Chemotherapy consisting of folinic acid,fluorouracil,and oxaliplatin was administered for three cycles,and was changed to gemcitabine monotherapy because of adverse effects and increased serum tumor marker levels.The patient remained asymptomatic during a 12-month follow-up.CONCLUSION Pancreatic heterotopy should be considered as source of a potentially malignant lesion,and early treatment or close monitoring for aberrant pancreas is recommended.展开更多
Aspergillus versicolor was isolated from the gastric juice of patients with chronic stomach diseases in high-risk area of gastric cancer. Mice fed with Aspergillus-inoculated corn flour developed adenocarcinoma of the...Aspergillus versicolor was isolated from the gastric juice of patients with chronic stomach diseases in high-risk area of gastric cancer. Mice fed with Aspergillus-inoculated corn flour developed adenocarcinoma of the lung in 15 of 35 mice (42.9%) and atypical hyperplasia of the glandular stomach in 13 of 35 mice (37.4%). Sterigmatocystin was identified by high performance liquid chromato-graphy (HPLC) and fluorescence spectrophotometry in the extract of Aspergillus-inoculated corn flour. The results suggest that the mycotoxin Sterigmatocystin may play a potential role in carcinogenesis in human.展开更多
Objective Hepatoid adenocarcinoma of the stomach is exceedingly rare. Only a few cases have been reported worldwide. In this report, we describe our pathological findings along with a review of the literature to impro...Objective Hepatoid adenocarcinoma of the stomach is exceedingly rare. Only a few cases have been reported worldwide. In this report, we describe our pathological findings along with a review of the literature to improve our understanding of the disease and prevent misdiagnosis, as well as to provide evidence for its treatment and prognosis.Methods A 68-year-old male patient was admitted to our hospital(Dalian Municipal Central Hospital, Dalian, China) complaining of upper abdominal pain. Physical examination and regular laboratory blood tests showed no obvious abnormalities. A contrast-enhanced computed tomography scan displayed a 3.0 cm × 3.0 cm mass in the gastric antrum, but no metastasis was found in the adjacent organs.Results A radical gastrectomy was performed and postoperative histopathology showed a moderately differentiated adenocarcinoma with partial hepatoid adenocarcinoma.Conclusion Hepatoid adenocarcinoma of the stomach is a rare malignant neoplasm. The diagnostic criteria for hepatoid adenocarcinoma of the stomach depends mainly on the clinical, radiographic, and histopathological findings. Pathomorphology and immunohistochemical staining can be utilized to confirm the diagnosis.展开更多
BACKGROUND Alternative splicing(AS)increases the diversity of mRNA during transcription;it might play a role in alteration of the immune microenvironment,which could influence the development of immunotherapeutic stra...BACKGROUND Alternative splicing(AS)increases the diversity of mRNA during transcription;it might play a role in alteration of the immune microenvironment,which could influence the development of immunotherapeutic strategies against cancer.AIM To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma(STAD)from the database.The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.METHODS Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model.In STAD,2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions.Furthermore,the network of splicing factors and overallsurvival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.RESULTS An eleven-AS-signature prognostic model(CD44|14986|ES,PPHLN1|21214|AT,RASSF4|11351|ES,KIAA1147|82046|AP,PPP2R5D|76200|ES,LOH12CR1|20507|ES,CDKN3|27569|AP,UBA52|48486|AD,CADPS|65499|AT,SRSF7|53276|RI,and WEE1|14328|AP)was constructed and significantly related to STAD overall survival,immune cells,and cancer-related pathways.The differentially expressed immune-related genes between the high-and low-risk score groups were significantly enriched in cancer-related pathways.CONCLUSION This study provided an AS-related prognostic model,potential mechanisms for AS,and alterations in the immune microenvironment(immune cells,genes,and pathways)for future research in STAD.展开更多
BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH...BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.展开更多
基金the Natural Science Foundation of Hubei Province(no.2020CFB592).
文摘Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical symptoms closely resemble those of gastric adenocarcinoma.Because of its rarity,misdiagnosis and missed diagnoses are prevalent.Compared with gastric adenocarcinoma,HAS typically exhibits higher invasiveness and amore unfavorable prognosis.This review aimed to elaborate on the pathological features,potential mechanisms,clinical characteristics,diagnosis,and prognosis of HAS.The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.
基金the National Key Basic Research Program of China(No.2015CB5540007)the National Natural Science Foundation of China(No.81572413,No.81702386)+1 种基金the Fundamental Research Funds for the Central Universities(No.2017KFYXJJ256)Scientific and Technological Application Foundation Project of Wuhan(No.2015060101010044).
文摘Hepatoid adenocarcinoma of the stomach (HAS)is an extremely rare and unique gastric malignancy.The present study aimed to examine the relevance of the clinicopathological characteristics of HAS with patient prognosis.We retrospectively reviewed clinical data of 34 HAS patients treated at our institution between January 2010 and December 2016,as well as 294 cases reported prior to 2017 in research databases.Among these patients,45.6%(115/252)had lesions in the gastric antrum and 77.0%(235/305)were male.Elevated levels of serum alpha-fetoprotein (AFP)were detected in most patients(75/93,80.6%).Vascular invasion(199/286,69.6%),lymph node metastasis (222/283,78.4%),and preoperative distant metastasis (121/328,36.9%)were commonly observed.The 5-year disease-free survival (DFS)and disease-specific survival (DSS) were 20.7%and 29.2%,respectively.DFS and DSS of patients receiving neoadjuvant therapy were significantly higher than those of patients receiving postoperative adjuvant therapy [DFS:P<0.001, hazard ratio (HR)=-1.831,95%confidence interval (CI):0.060-0.429;DSS:P<0.001,HR=-2.185, 95%CI:0.032-0.401].In conclusion,HAS exhibits distinct clinicopathological characteristics and a strikingly worse prognosis when compared with common gastric cancer.Complete surgery,early pTNM stage,and adjuvant therapy may predict a more favorable prognosis.Neoadjuvant therapy is strongly recommended for patients with lymph node metastasis or/and preoperative distant metastasis.
文摘Hepatoid adenocarcinoma of the stomach (HAS) is a rare form of gastric cancer that has unique clinicopathological features and an extremely poor prognosis. Here, we report on three patients with suspected gastric cancer who were referred to our hospital. Gastrointestinal fiberscopy on the three patients revealed two lesions in the antrum and a third lesion in the gastroesophageal junction. The alpha fetoprotein (AFP) serum levels were markedly elevated in all cases. At the time of diagnosis, two cases were advanced stages with lymph nodes and/or liver metastases. Two patients underwent exploratory laparotomy. A total gastrectomy was performed on the operable lesion, and an expanded gastrectomy was completed in the case with hepatic metastases. Histopathological analysis revealed that the tumors displayed two pathological changes:hepatoid-like foci and adenocarcinomatous. Furthermore, the tumor cells were immunohistochemically positive for AFP, alpha-1 antitrypsin, and alpha-1 antichymotrypsin. All three patients received chemotherapy. The follow-up duration ranged from 8-36 mo. Our experience and previous published studies have suggested that HAS is an aggressive type of adenocarcinoma. However, radical surgery and chemotherapy may positively impact clinical outcomes.
文摘BACKGROUND The aim of the present study was to examine the clinical characteristics of hepatoid adenocarcinoma of the stomach (HAS) and its diagnosis,treatment,and prognosis.CASE SUMMARY A retrospective analysis of 13 HAS cases was performed.The mean age of the 13patients was 66.08 years,and 10 of the 13 patients were male.Prior to treatment,the alpha-fetoprotein levels in the serum were elevated in 7 patients,the tumour was located in the distal or gastric body in 11 patients,and the gastroscopy pathological results showed that 3 patients had poorly differentiated tumours and that 8 patients had moderately/poorly differentiated tumours.Abdominal CT scans showed local stomach wall thickening,and enlarged lymph nodes were visible around the stomach in 8 patients.Of the 13 patients,11 underwent radical surgery.The clinical pathological staging was as follows:Stage Ⅱ in 2 cases;stage Ⅲ in 8 cases;and stage Ⅳ in 1 case.A total of 3 patients were lost to follow-up.Otherwise,as of the last follow-up,3 patients had survived for 56 mo,and the other 7 patients failed to achieve long-term survival (survival period of 1-56 mo).CONCLUSION HAS is a special type of gastric cancer,and the prognosis of HAS has improved compared with past prognoses.Measurement of alpha-fetoprotein,early diagnosis,active surgical treatment,and application of new diagnostic and treatment techniques are conducive to improving the prognosis of HAS.
文摘AIM: To evaluate the dynamic computed tomography(CT) findings of liver metastasis from hepatoid adenocarcinoma of the stomach(HAS) and compared them with hepatocellular carcinoma(HCC).METHODS: Between January 2000 and January 2015, 8 patients with pathologically proven HAS and liver metastases were enrolled. Basic tumor status was evaluated for the primary tumor location and metastatic sites. The CT findings of the liver metastases were analyzed for tumor number and size, presence of tumor necrosis, hemorrhage, venous tumor thrombosis, and dynamic enhancing pattern.RESULTS: The body and antrum were the most common site for primary HAS(n = 7), and observed metastatic sites included the liver(n = 8), lymph nodes(n = 7), peritoneum(n = 4), and lung(n = 2). Most of the liver metastases exhibited tumor necrosis regardless of tumor size. By contrast, tumor hemorrhage was observed only in liver lesions larger than 5 cm(n = 4). Three patterns of venous tumor thrombosis were identified: direct venous invasion by the primary HAS(n = 1), direct venous invasion by the liver metastases(n = 7), and isolated portal vein tumor thrombosis(n = 2). Dynamic CT revealed arterial hyperattenuation and late phase washout in all the liver metastases.CONCLUSION: On dynamic CT, liver metastasis from HAS shared many imaging similarities with HCC. For liver nodules, the presence of isolated portal vein tumor thrombosis and a tendency for tumor necrosis are imaging clues that suggest the diagnosis of HAS.
基金Research Fund of Basic Research Project of Shenzhen(Natural Science Foundation of Shenzhen),No.JCYJ20230807142205010.
文摘BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatment plan needs further study.CASE SUMMARY In order to deeply understand the occurrence and development of HAL,here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation.The patient refused chemotherapy and received one course of treatment(immune checkpoint inhibitors),and died three months later due to progressive disease.CONCLUSION HAL is a special type of NSCLC.The surgical treatment of HAL in the limited stage can achieve long-term survival,but most of them were in the advanced stage when they were found,and the prognosis was poor,which requires multidisciplinary comprehensive treatment.
基金Supported by The Medical and Health Research Project of Zhejiang Province,No.2021RC097.
文摘BACKGROUND Stomach adenocarcinoma(STAD)is one of the main reasons for cancer-related deaths worldwide.This investigation aimed to define the connection between STAD and Cuproptosis-related genes(CRGs).Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper.AIM To explore the identification of potential biomarkers for STAD disease based on cuproptosis.METHODS A predictive model using Gene Ontology(GO),Least Absolute Shrinkage and Selection Operator(LASSO),Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Set Variation Analysis(GSVA),and Gene Set Enrichment Analysis analyzed gene interconnections,focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD.Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed.The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic,Kaplan-Meier curves,and COX regression analysis.Validation was conducted with datasets GSE26942,GSE54129,and GSE66229.Expression of copper-related differ-entially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas.RESULTS Three significant genes(FDX1,LIAS,MTF1)were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups.These genes were down-regulated in both risk categories.GO and KEGG analyses highlighted their involvement mainly in the electron transport chain.After validating their differential expression,FDX1 emerged as the most accurate diagnostic marker for gastric cancer.Additionally,the RCircos package localized FDX1 on chromosome 11.CONCLUSION Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy,providing new ideas for further scientific research.
文摘Objective:We reported a case with AFP produced gastric hepatoid adenocarcinoma.Methods:A male patient,77 year-old,was admitted to our hospital due to an unreasonable elevation of serum AFP.The tumors were revealed by PET-CT,but until the tumors were removed during the surgery,we did not recognize the primary lesion was the gastric cancer.Results:Radical distal gastrectomy was performed.The gastric lesion was confirmed by histology as a hepatic adenocarcinoma in its early stage.Conclusion:The rare etiology of the AFP elevation should be kept in mind in clinic,extrahepatic lesions should be excluded.
文摘BACKGROUND Both hepatoid adenocarcinoma of the stomach(HAS)and neuroendocrine differentiation(NED)are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes.HAS with NED is even rarer.CASE SUMMARY Here,we report a 61-year-old man with HAS with NED,as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule.Distal gastrectomy was performed,and pathological examination led to the diagnosis of HAS with NED.However,liver metastases occurred 6 mo later despite adjuvant chemotherapy,and the patient died 27 mo postoperatively.CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases.We first report the detailed processes of the treatment and development of HAS with NED,providing an important reference for the clinical diagnosis and treatment of this condition.
文摘We describe the computed tomography(CT)imaging findings in six cases(five males and one female;age range 61-78 years;mean age 67.3 years)with histologically proven hepatoid adenocarcinoma of the stomach(HAS).Five of the six patients had elevated serum alpha-fetoprotein levels.The most common type of gross appearance HAS on CT is a polypoid mass(83%,5/6).The most common contrast enhancement pattern was heterogeneous.All six patients had a regional lymphadenopathy larger than 6 mm in its short axis.Liver metastases(n=3)were noted.Venous tumor thrombosis was identified in the portal vein(n=2)of the regions near primary gastric tumors or metastatic masses.Our findings suggest in an elderly,male patients with a large heterogeneous enhancement tumor,the presence of distant metastases,regional lymphadenopathy and characteristically increased serum alphafetoprotein levels indicates a high likelihood of HAS.
文摘A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease(PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon,who was initially treated with a subtotal colectomy with ileostomy.One year later,the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis,as well as a markedly elevated serum level of alpha-fetoprotein(AFP).Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid adenocarcinoma.Subsequent review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic adenocarcinoma.The patient was subsequently treated with a cytotoxic regimen of FOLFOX(oxaliplatin,leucovorin,5-fluorouracil) and bevacizumab,with stable results being achieved after six months.This case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.
基金Supported by Grants-in-aid for Cancer Research from the Ministry of Education, Science and Culture, Japan and the Fukuoka Cancer Society, Fukuoka, Japan
文摘AIM: Minimal deviation carcinoma of the uterine cervix, otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive behavior. In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA, we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products. METHODS: Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT: Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion, lymph node metastasis was not present and none of the patients died of the lesions (mean follow-up period, 56 too). All 9 cases of EWDA could be classified into gastric phenotype (5 lesions) and intestinal phenotype (4 lesions). The former resembled gastric foveolar epithelium, mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cellsand their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein. CONCLUSION: Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c-erbB-2 protein over-expression. Because of its resemblance to normal gastric mucosa or mucosa with intestinal metaplasia, EWDA is often misdiagnosed. To prevent the misdiagnosis of such lesions, the clinical and pathologic characteristics should be taken into consideration.
基金Supported by Shanghai Education Committee Foundation, No.024119114
文摘AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.
文摘BACKGROUND Hepatoid adenocarcinoma of the lung(HAL) is an extremely rare malignant tumor,and many patients with HAL exhibit high levels of alpha-fetoprotein(AFP) expression.Currently,there is no standardized treatment strategy for advanced HAL and its prognosis is poor.CASE SUMMARY We report a 55-year-old man with unresectable AFP-related HAL.The largest cross-sectional area of the mass in the upper lobe of the left lung at the beginning of treatment was 8.46 cm × 6.53 cm.The patient’s serum AFP level was 9283 ng/m L.The mass increased in size to 8.86 cm × 8.21 cm after two courses of platinum-based combination chemotherapy and immunotherapy,and serum AFP reached its highest level(71232.2 ng/m L).The patient was treated with sorafenib(400 mg twice daily,per os).Forty days later,the mass was reduced to 5.63 cm × 5.29 cm and serum AFP level dropped to 786.8 ng/m L.The patient achieved partial remission for > 9 mo with sorafenib and an excellent biomarker response,as well as survival > 13 mo,which is among the longest reported for unresectable stage IV HAL.CONCLUSION This is the first report to document successful treatment of unresectable AFPrelated HAL with single-agent sorafenib after multiline therapy.
文摘BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is currently no standard treatment for this disease,which has a poor prognosis.CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis.He underwent first-line chemotherapy but that failed.Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment.The progression-free survival and overall survival were 14 mo and 16 mo,respectively,after treatment.In addition,the main adverse reaction was tolerable.The patient did not die of tumor progression.CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment.Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.
基金The authors thank Mr.Yong-Jian Deng,Department of Pathology,Nanfang Hospital。
文摘BACKGROUND Heterotopic pancreas is a common lesion found in the gastrointestinal tract and is usually considered a benign disease.Reports of malignant change of heterotopic pancreas are scarce.CASE SUMMARY A 44-year-old Chinese female underwent a gastroscopy to assess abdominal distension that had persisted for 2 months.A protruding lesion in the gastric antrum was revealed but no malignant tissue was found in the biopsy specimen.The patient's symptom persisted and progressed to repeated vomiting.Endoscopy after 4 months revealed obstruction of the gastric outlet caused by the protruding lesion.A distal gastrectomy was performed.Histopathological examination of the surgical specimen showed the malignant transformation of aberrant pancreas in the stomach.Chemotherapy consisting of folinic acid,fluorouracil,and oxaliplatin was administered for three cycles,and was changed to gemcitabine monotherapy because of adverse effects and increased serum tumor marker levels.The patient remained asymptomatic during a 12-month follow-up.CONCLUSION Pancreatic heterotopy should be considered as source of a potentially malignant lesion,and early treatment or close monitoring for aberrant pancreas is recommended.
文摘Aspergillus versicolor was isolated from the gastric juice of patients with chronic stomach diseases in high-risk area of gastric cancer. Mice fed with Aspergillus-inoculated corn flour developed adenocarcinoma of the lung in 15 of 35 mice (42.9%) and atypical hyperplasia of the glandular stomach in 13 of 35 mice (37.4%). Sterigmatocystin was identified by high performance liquid chromato-graphy (HPLC) and fluorescence spectrophotometry in the extract of Aspergillus-inoculated corn flour. The results suggest that the mycotoxin Sterigmatocystin may play a potential role in carcinogenesis in human.
文摘Objective Hepatoid adenocarcinoma of the stomach is exceedingly rare. Only a few cases have been reported worldwide. In this report, we describe our pathological findings along with a review of the literature to improve our understanding of the disease and prevent misdiagnosis, as well as to provide evidence for its treatment and prognosis.Methods A 68-year-old male patient was admitted to our hospital(Dalian Municipal Central Hospital, Dalian, China) complaining of upper abdominal pain. Physical examination and regular laboratory blood tests showed no obvious abnormalities. A contrast-enhanced computed tomography scan displayed a 3.0 cm × 3.0 cm mass in the gastric antrum, but no metastasis was found in the adjacent organs.Results A radical gastrectomy was performed and postoperative histopathology showed a moderately differentiated adenocarcinoma with partial hepatoid adenocarcinoma.Conclusion Hepatoid adenocarcinoma of the stomach is a rare malignant neoplasm. The diagnostic criteria for hepatoid adenocarcinoma of the stomach depends mainly on the clinical, radiographic, and histopathological findings. Pathomorphology and immunohistochemical staining can be utilized to confirm the diagnosis.
基金the National Clinical Key Specialty Construction Program of China and Grants from the National Science Foundation Project of the Fujian Science and Technology Department,No.2017J01264 and No.2018Y0015the Foundation for Fujian Provincial Health Technology Project,No.2019-ZQN-16,No.2019-CXB-9,and No.2019006the Startup Fund for Scientific Research,Fujian Medical University,No.2017Q1219 and No.2017Q1220.
文摘BACKGROUND Alternative splicing(AS)increases the diversity of mRNA during transcription;it might play a role in alteration of the immune microenvironment,which could influence the development of immunotherapeutic strategies against cancer.AIM To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma(STAD)from the database.The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.METHODS Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model.In STAD,2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions.Furthermore,the network of splicing factors and overallsurvival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.RESULTS An eleven-AS-signature prognostic model(CD44|14986|ES,PPHLN1|21214|AT,RASSF4|11351|ES,KIAA1147|82046|AP,PPP2R5D|76200|ES,LOH12CR1|20507|ES,CDKN3|27569|AP,UBA52|48486|AD,CADPS|65499|AT,SRSF7|53276|RI,and WEE1|14328|AP)was constructed and significantly related to STAD overall survival,immune cells,and cancer-related pathways.The differentially expressed immune-related genes between the high-and low-risk score groups were significantly enriched in cancer-related pathways.CONCLUSION This study provided an AS-related prognostic model,potential mechanisms for AS,and alterations in the immune microenvironment(immune cells,genes,and pathways)for future research in STAD.
基金Supported by the Science and Technology Program of Liaoning Province,No.2021-MS-040.
文摘BACKGROUND The carcinogenesis of stomach adenocarcinoma(STAD)involves many different molecules and multiple pathways,including the NOTCH signaling pathway.As a key factor that functions as a critical link in the NOTCH pathway,mind bomb 1(MIB1)is upregulated in various tumors and has been reported to promote cell metastasis and invasion.However,studies on the role of MIB1 in STAD are limited.Here,we evaluated the prognostic value of MIB1 in STAD and its association with immune infiltration and copy number variation.AIM To elucidate the relationship between MIB1 gene and gastric cancer(GC)and provide a new idea for the treatment of GC.METHODS We identified mutations in the MIB1 gene by searching the cBioPortal database and then analyzed their relationship with the overall survival rate and diseasefree survival rate using the Kaplan-Meier method.The Cancer Genome Atlas(TCGA)database provided transcript levels for MIB1 in STADs and normal tissues.As a method of distinguishing the STAD tissues from adjacent normal tissues,a receiver operating characteristic(ROC)curve was generated.Kaplan-Meier plotter was used to determine the effect of MIB1 expression on survival.Based on the LinkedOmics database,we were able to identify the coexpressed genes of the MIB1 gene,the top 50 positively correlated genes,and the top 50 negatively correlated genes.STRING was used to construct protein-protein interaction networks related to the MIB1 gene.An analysis of functional enrichment was carried out using the R package“Cluster Profiler”.The relationships between mRNA expression of MIB1 and immune infiltrates were assessed by Tumor IMmune Estimation Resource(TIMER)and the“GSVA package”in R.RESULTS According to the cBioPortal database,the MIB1 mutation rate in 287 patients in the TCGA dataset was approximately 6%.Kaplan-Meier survival analysis showed that patients with STAD in the mutated group had a worse prognosis than those in the unmutated group(P=0.0156).There was a significant upregulation of MIB1 expression in STAD tissues compared to adjacent normal tissues.A high T stage was associated with increased MIB1 mRNA expression.The ROC curve analysis revealed 59.4%sensitivity and 85.6%specificity of MIB1 for differentiating STAD tissues from adjacent normal tissues at a truncation level of 2.248.Kaplan-Meier plotter indicated that patients with higher MIB1 levels had a worse prognosis than those with lower levels(26.4 mo vs 56.2 mo,P=0.0330).A correlation analysis demonstrated an association between immune infiltrates and MIB1 mRNA expression.CONCLUSION Upregulation of MIB1 expression is significantly associated with poor survival rate and immune infiltration in gastric adenocarcinoma.MIB1 may be a biomarker for the poor prognosis of STAD patients and a potential immunotherapeutic target.